CN107445938A - Crystal form, preparation method and the Pharmaceutical composition containing the crystal form of the tartrates of Yi Ligelusita half - Google Patents
Crystal form, preparation method and the Pharmaceutical composition containing the crystal form of the tartrates of Yi Ligelusita half Download PDFInfo
- Publication number
- CN107445938A CN107445938A CN201610375158.6A CN201610375158A CN107445938A CN 107445938 A CN107445938 A CN 107445938A CN 201610375158 A CN201610375158 A CN 201610375158A CN 107445938 A CN107445938 A CN 107445938A
- Authority
- CN
- China
- Prior art keywords
- ligelusita
- crystal form
- mixed solution
- preparation
- tartrates
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The present invention provides a kind of crystal form of half tartrate of the Yi Ligelusita as shown in Formulas I (a), its preparation method and the pharmaceutical composition containing the crystal form, the X ray powder diffractions of the crystal form of half tartrate of the Yi Ligelusita are 10.2 ° at 2 θ angles, 12.4 °, 13.6 °, 14.9 °, 20.1 °, there is principal character peak at 22.1 °, DSC collection of illustrative plates, which is shown in 161 DEG C ~ 162 DEG C, endothermic peak, the Yi Ligelusita of the crystal form half tartrate has the advantages of stability is good, obtained pharmaceutical composition has the advantages of stripping property is good, the crystal is suitable as the production and storage that bulk drug is used for pharmaceutical preparation.
Description
Technical field
The present invention relates to the crystal form of the tartrates of Yi Ligelusita half, preparation method and contain the crystal form
Medical composition and its use, belong to pharmaceutical technology field.
Background technology
Yi Ligelusita (Eliglustat), the entitled N- of chemistry [(dislike (1R, 2R) -1- by 2,3- dihydros-Isosorbide-5-Nitrae-benzo two
Alkane -6- bases) -2- hydroxyls -1- (1- pyrrolidinomethyls) ethyl] caprylamide, be it is a kind of be used for treat the first of specific I types Gaucher disease
Micromolecular compound, its structural formula is shown in formula I：
Rare disease class known to the whole world accounts for the 10% of human diseases up to 7000 kinds, and China has found that disease is 5781 kinds,
Patient exceedes ten million.Dagger-axe Xie Shi diseases (Gaucher ' s disease) are a kind of rare diseases of the most common heredity of lysosomal storage disease
Disease, it is because β-glucocerebrosidase is reduced or is lacked, glucocerebroside is largely deposited in mononuclear phagocyte system,
Histocyte is caused largely to be bred.According to the urgency of dagger-axe Xie Shi disease morbidities is slow, internal organ involved and whether there is neurological symptom,
I types, II type, the type of III type 3 are divided into, wherein I types disease is most common type, accounts for the 94% of dagger-axe Xie Shi diseases, youngster
Tong Yucheng can fall ill per capita, and more with preschool child hair patient, onset is slow, course of disease length.Dagger-axe Xie Shi diseases have all over the world
Fall ill, the incidence of disease has very big difference in different groups.Traditionally, it is a kind of main disease for influenceing Ashkenazim adult
Disease, but I type dagger-axe Xie Shi patient of the discovered in recent years more than 50% was diagnosed before 20 years old, and institute may be influenceed
There is ethnic group.I type dagger-axe Xie Shi diseases global incidence is 1/50000~1/100000, and China's incidence of disease is 1/200000~1/
500000, patient about 7000 or so, fallen ill more in birth or children, show as the lipidosis of multisystem, involve marrow,
Liver and spleen, bone and nervous system, pain, bone injury can be caused even dead, feature is liver and spleen enlargement and other devices
The dysfunction of official, the visible influence to brain in a small number of cases, if but find treatment in time early, patient can normal life.
The existing treatment means of dagger-axe Xie Shi diseases include：Symptomatic treatment, splenectomy, enzyme replacement therapy (ERT) and candidate stem cell
Transplantation treatment, wherein enzyme replacement therapy (ERT) are treatment I type Gaucher disease most efficient methods at present, but patient need to determine all the life
Phase (injection in every 2 weeks is once) receives venoclysis, and expense is sufficiently expensive so that domestic patient home need to bear high treatment
Expense, therefore, most of patient still in diagnose it is poor, without medicine cure state.
Yi Ligelusita is the first small molecule oral drugs for treating dagger-axe Xie Shi diseases, is grown up as specific I types Gaucher disease
The line oral therapies of patient.Yi Ligelusita is a kind of potent, high degree of specificity ceramide-analogous inhibitor, is targetted
Glucosylceramide synthase (GCS), the generation and accumulation of glucose ceramide can be reduced.The medicine is not yet in state at present
Interior listing.As the first oral therapeutic drug of I type dagger-axes Xie Shi diseases, the medicine clinical practice is convenient, is currently relied upon overturning completely
The Gaucher disease market structure of injection-type medicine, the uniqueness and very important new practicality for turning into I type Gaucher diseases colony are controlled
Treat selection.The compassion that research and development and listing of the medicine in China also will fundamentally change domestic dagger-axe Xie Shi patients and can be cured without medicine at present
Miserable situation, turn into the revolutionary medicine of the treatment dagger-axe Xie Shi diseases in China, there is greatly social benefit and exploitation necessity.
A kind of crystal form of the tartrates of Yi Ligelusita half is disclosed in patent CN201080061535.It is single
There is different crystal forms and be referred to as polymorphism in compound, this is the critical nature of compound, for most compounds, typically
Polymorphism all be present, and the different crystal formations of same drug are for the stability of medicine, homogeneity, bioavilability and system
Agent production etc. has important influence.Polymorph each has different physical properties, such as different dissolution properties, difference
Fusing point and/or different X-ray diffraction peaks.Therefore, when a kind of medicine has polytropism, it is necessary to brilliant to it
Type is furtherd investigate.
Because the solubility of every kind of polymorph can be different, for providing the medicine with predictable dissolution properties
The presence for differentiating pharmaceutical polymorphs for compositions is important.Study all solid-state forms of medicine including all more
Stability, dissolubility and the mobility of crystal formation thing, pseudopolymorph and hydrate and the every kind of polymorph of measure are desired
's.The discovery of the new polymorph of pharmaceutically acceptable compound provides the new chance for the performance characteristic for improving drug products.It expands
What big formulation science man was possessed be available for designing such as medicine have Targeting delivery property or it is other needed for characteristic medicine
The material storehouse of formulation.Therefore, the new crystalline forms of existing medicine are researched and developed, to improve its preparation, play its clinic
Advantage, it is that current pharmaceutical industry walks one of road of autonomous innovation.
The present invention provides a kind of crystal form of the new tartrates of Yi Ligelusita half, and the crystal form has stable
The advantages of property is good, and placing relevant material for a long time does not increase, and clarity does not decline, obtained pharmaceutical composition has biological utilisation
The advantages that degree is high, stripping property is good, it is suitable as production and storage that bulk drug is used for pharmaceutical preparation.
The content of the invention
It is an object of the present invention to provide it is easily fabricated and prepare, to light, wet, good thermal stability, suitable for industrialization
The crystal form of the new tartrates of Yi Ligelusita half of production and storage.
It is a further object to provide the preparation side of the crystal form of the tartrates of Yi Ligelusita half
Method.
It is also another object of the present invention to provide the pharmaceutical composition containing the crystal form.
Object of the present invention is reached by following design：
The present invention provides a kind of new crystal form of the tartrates of Yi Ligelusita half as shown in following formula I (a), preferably
, the crystal form is to have main X-ray powder at 10.2 °, 12.4 °, 13.6 °, 14.9 °, 20.1 °, 22.1 ° at 2 θ angles
Last diffraction maximum.
According to Yi Ligelusita of the present invention half tartrate crystal form, more preferred, the crystal form
Have at 2 θ angles is 7.4 °, 10.2 °, 12.4 °, 13.6 °, 14.9 °, 18.4 °, 19.0 °, 20.1 °, 20.8 °, 22.1 ° main
X-ray powder diffraction peak.
According to Yi Ligelusita of the present invention half tartrate crystal form, wherein, half tartrate
Refer to the tartrates of L- half.
Preferably, the DSC collection of illustrative plates of the crystal form, which is shown at 161 DEG C~162 DEG C, endothermic peak.
The method for preparing the tartrate crystal forms of Yi Ligelusita half of the present invention, its preferable step is such as
Under, mixed solution is prepared, takes a certain amount of L-TARTARIC ACID to be dissolved in a certain amount of mixed solution, is heated to solid dissolving；One is taken again
Quantitative Yi Ligelusita is dissolved in another a certain amount of mixed solution, and above-mentioned L-TARTARIC ACID solution is added dropwise, at room temperature stirring analysis
Crystalline substance, filtering, is drying to obtain.
Preferably, any two kinds in methanol, acetone, water, ethanol, isopropanol of the mixed solution.
Preferably, one kind in the mixed solution is acetone soln.
It is further preferred that the mixed solution is the mixed solution of water and acetone.
Preferably, the vacuum drying temperature is 50-70 DEG C.
Present invention also offers a kind of pharmaceutical composition, and it includes above-mentioned crystal, and pharmaceutically acceptable carrier.Medicine
Compositions can use conventional solid or liquid-carrier or diluent and the medicine of the type suitable for expected method of application
Additive is prepared.
The pharmaceutical composition of the tartrate crystal forms of Yi Ligelusita half comprising the present invention can also include one kind
Or a variety of pharmaceutically acceptable excipients, they are preferably selected from filler, buffer, glidant, flowable, lubricant, preservative, surface
Activating agent, wetting agent, adhesive, disintegrant and thickener.Known other figurations in field of medicinal compositions can also be used
Agent.Moreover, pharmaceutical composition can also include two or more members for falling within above-mentioned set.
The tartrate crystal forms of Yi Ligelusita half of the present invention are illustrated below by way of data.
The tartrates of Yi Ligelusita half crystallization of Example 3, using x-ray powder diffraction instrument (Germany
Bruker D8-advance), Cu targets, pipe presses 40kv, and what is measured under pipe stream 40mA is represented with 2 θ angles and interplanar distance (d values)
X-ray powder diffraction spectrum as shown in Figure 1, its data is as follows：
| Angle (2 θ °) | D values (angstrom) | Relative intensity I (%) |
| 5.309 | 16.63236 | 10.2% |
| 6.165 | 14.32367 | 16.9% |
| 7.407 | 11.92542 | 30.7% |
| 10.174 | 8.68779 | 37.7% |
| 10.644 | 8.30512 | 5.9% |
| 11.852 | 7.46073 | 5.1% |
| 12.400 | 7.12360 | 48.6% |
| 13.566 | 6.52205 | 37.3% |
| 14.878 | 5.94978 | 48.0% |
| 15.491 | 5.71556 | 16.7% |
| 15.898 | 5.57001 | 22.6% |
| 16.295 | 5.43535 | 21.6% |
| 16.741 | 5.29138 | 9.2% |
| 17.112 | 5.17744 | 12.7% |
| 17.608 | 5.03284 | 18.4% |
| 17.989 | 4.92721 | 17.3% |
| 18.379 | 4.82333 | 27.2% |
| 18.649 | 4.75409 | 17.9% |
| 18.985 | 4.67074 | 27.5% |
| 19.456 | 4.55878 | 17.5% |
| 19.844 | 4.47052 | 18.7% |
| 20.106 | 4.41278 | 34.4% |
| 20.442 | 4.34096 | 8.3% |
| 20.838 | 4.25941 | 28.9% |
| 22.118 | 4.01568 | 99.5% |
| 23.634 | 3.76146 | 11.1% |
| 23.898 | 3.72050 | 20.3% |
| 24.168 | 3.67961 | 14.2% |
| 24.405 | 3.64437 | 8.8% |
| 25.312 | 3.51586 | 10.0% |
| 25.838 | 3.44535 | 9.0% |
| 30.363 | 2.94149 | 6.5% |
Example 3 the tartrates of Yi Ligelusita half crystallization, its differential scanning figure (DSC) as shown in Figure 2, the crystal
There is endothermic transition at 161 DEG C~162 DEG C, heat absorption start temperature is at 161 DEG C.
The tartrates of Yi Ligelusita half crystallization of Example 3, high temperature 10 days, resulting at 105 DEG C
HPLC (testing conditions：Shimadzu liquid phase, mobile phase：Na2HPO4/H3PO4, pH：5, wavelength 210nm, flow velocity 1.0ml/min, sample introduction
Measure 10 μ L) collection of illustrative plates as shown in Figure 3, data such as following table, collection of illustrative plates shows the crystalline content still more than 99.8%, single miscellaneous to be less than
0.1%, impurity number is 3.
HPLC accompanying drawing data
| Peak | Retention time | Area % | Separating degree |
| 1 | 3.949 | 0.013 | 0.000 |
| 2 | 8.302 | 0.029 | 19.179 |
| 3 | 21.789 | 0.068 | 34.983 |
| 4 | 22.620 | 99.890 | 1.222 |
| Amount to | 100.000 |
The capsule of the 3 batches of made tartrates of Yi Ligelusita half crystallizations containing the present invention of Example 4, and commercially available original
Triturate (Eliglustat, trade nameManufacturer Genzyme Corporation), carry out dissolution rate control and survey
(condition is for examination：Slurry processes, pH1.0 hydrochloric acid solutions, dissolution fluid volume 900mL, rotating speed 75rpm, sample volume 10mL, detection：
280nm, ultraviolet specrophotometer measure absorbance), its respective dissolution data is as follows：
From data as can be seen that crystallizing the dissolution of produced capsule using the tartrates of Yi Ligelusita half of the present invention
Degree is fine, and dissolution in 15 minutes reaches can complete dissolution within more than 95%, 1 hour.
Brief description of the drawings
Fig. 1：The X-ray powder diffraction figure of the tartrate crystal forms of Yi Ligelusita half of the present invention；
Fig. 2：The DSC differential scanning figures of the tartrate crystal forms of Yi Ligelusita half of the present invention；
Fig. 3：The tartrates of Yi Ligelusita half of the present invention crystallize the figures of the HPLC after high temperature.
Specific embodiment
Embodiment 1：Referenced patent CN201510703628.2 embodiment, Yi Ligelusita is synthesized, specific steps are such as
Under.
The preparation of formula 1. (III) compound
In the 5L round bottom there-necked flasks equipped with drying tube, formula (II) compound (278g, 1mol) and acetonitrile (2.8L), stirring are added
Lower addition potassium carbonate (276g, 2mol), outer 10 DEG C of acetonitrile (300mL) solution that Boc acid anhydrides (327g, 1.5mol) is added dropwise of bath, adds
Continue to react 3h after complete, then add water (3L), with ethyl acetate (800mL × 3) extraction three times, merge organic phase, use saturation
Saline solution (800mL) washs, anhydrous sodium sulfate drying, filters, and concentration, obtains pale yellow oil 368g, yield 97.6%.
The preparation of formula 2. (IV) compound
In the 5L round bottom there-necked flasks equipped with drying tube, formula (III) compound (302g, 0.8mol) and DMF (3.6L) are added, is stirred
After mixing dissolving, potassium carbonate (276g, 2mol), bromobenzyl (205g, 1.2mol) are sequentially added, outer 160 DEG C of bath continues to react 7h, cold
But, incline into water (20L), with ethyl acetate (2L × 3) extraction three times, merge organic phase, eaten successively with water (2L × 5), saturation
Salt solution (2L) is washed, anhydrous sodium sulfate drying, is filtered, and concentration, obtains yellow oil 318g, yield 85.1%.
The preparation of formula 3. (V) compound
In the 3L round bottom there-necked flasks equipped with drying tube, formula (IV) compound (280g, 0.6mol) and tetrahydrofuran are added
(2.2L), after stirring and dissolving, 4N aqueous hydrochloric acid solutions (300mL, 1.2mol) are added, room temperature continues to react 2h, adds water 2L, decompression
Concentration boils off tetrahydrofuran, with ethyl acetate (500mL × 3) extraction three times, merges organic phase, successively with water (500mL), saturation
Saline solution (500mL) is washed, anhydrous sodium sulfate drying, is filtered, and concentration, obtains yellow oil 208g, yield 94.2%.
The preparation of formula 4. (VI) compound
In the 3L round bottom there-necked flasks equipped with drying tube, formula (V) compound (184g, 0.5mol) and dichloromethane are added
(1.8L), after stirring and dissolving, triethylamine (71g, 0.7mol), caprylyl chloride (97g, 0.6mol) being added, room temperature continues to react 28h,
Water 2L is added, with ethyl acetate (500mL × 3) extraction three times, merges organic phase, successively with water (500mL), saturated aqueous common salt
(500mL) is washed, anhydrous sodium sulfate drying, is filtered, and concentration, obtains yellow oil 199g, yield 80.6%.
The preparation of formula 5. (I) compound
In 3L round bottom there-necked flasks, formula (VI) compound (198g, 0.4mol) and 10% glacial acetic acid methanol solution (1.9L) are added,
After stirring and dissolving, 10% palladium carbon (9.9g) is added, normal pressure hydrogenation 18h at interior 50 DEG C of temperature, filtering, filtrate concentration, adds water (2L),
PH=9~10 are adjusted with 2N sodium hydroxides, with ethyl acetate (500mL × 3) extraction three times, merges organic phase, uses water successively
(500mL), saturated aqueous common salt (500mL) are washed, anhydrous sodium sulfate drying, filter, concentration, obtain yellow solid (formula (I) compound,
That is Yi Ligelusita), dissolved with acetone (1.3L), add L-TARTARIC ACID (60g, 0.4mol), stir 16h, filtered, filter cake is used
Acetone washs, and vacuum drying, obtains off-white powder (i.e. Yi Ligelusi tartrates) 139g, yield 62.9%.
Embodiment 2：Prepare the tartrate salt crystals of Yi Ligelusita half
At room temperature, the Yi Ligelusita obtained by Example 1 (10g/24.7mmol) is dissolved in 140ml methanol/acetones (v/v：
0.05:0.95) in solution.L-TARTARIC ACID (1.84g/12.3mmol) is taken to be added to 60ml methanol/acetone (v/v：0.05:0.95)
In solution, 40 DEG C are heated to, solid is entirely molten, and this solution is added dropwise in former solution.After being stirred at room temperature ten minutes, have a small amount of solid
Body is slowly separated out, and a large amount of solids separate out after 15 minutes, are filtered after being stirred for 3 hours, and filter cake is eluted with acetone 20ml*2, solid
16-20 hours are dried in vacuo at 50 DEG C, obtain off-white powder 9.18g, yield 77.5%.
Embodiment 3：Prepare the tartrate salt crystals of Yi Ligelusita half
At room temperature, the Yi Ligelusita obtained by Example 1 (10g/24.7mmol) is dissolved in 140ml water/acetone (v/v：
0.01:0.99) in solution.L-TARTARIC ACID (1.84g/12.3mmol) is taken to be added to 60ml water/acetone (v/v：0.01:0.99) solution
In, 40 DEG C are heated to, solid is entirely molten, and this solution is added dropwise in former solution.After being stirred at room temperature ten minutes, there are a large amount of solids fast
Speed separates out, and is filtered after being stirred for 3 hours, is eluted with acetone 2*20ml, and solid is dried in vacuo 16-20 hours at 60 DEG C, and it is white to obtain class
Color solid 9.78g, yield 82.5%.
Embodiment 4：Prepare the Capsule technologies (1000) of the tartrate salt crystals of Yi Ligelusita half containing the present invention
The tartrate salt crystals of Yi Ligelusita half obtained by 100g embodiments 3 are taken, with 44.6g MCCs, 44.6g mono-
Water and milk sugar, 8.1g HPMC E50s, were mixed together 60 mesh sieves, were mixed 3 minutes in wet granulator high speed,
Add suitable quantity of water and prepare softwood, the granulation of 20 eye mesh screens is crossed using oscillating granulator, after drying, adds 2.7g Compritol 888 ATOs,
Mixed 5 minutes in three-dimensional mixer, capsule is filled with capsule filling machine.
Claims (10)
- A kind of 1. half tartrate crystal form of Yi Ligelusita as shown in Formulas I (a), it is characterised in that the crystallization Form is to have main X-ray powder diffraction peak at 10.2 °, 12.4 °, 13.6 °, 14.9 °, 20.1 °, 22.1 ° at 2 θ anglesI(a)。
- 2. Yi Ligelusita as claimed in claim 1 half tartrate crystal form, it is characterised in that the crystalline Formula is to have mainly at 7.4 °, 10.2 °, 12.4 °, 13.6 °, 14.9 °, 18.4 °, 19.0 °, 20.1 °, 20.8 °, 22.1 ° at 2 θ angles X-ray powder diffraction peak.
- 3. Yi Ligelusita as claimed in claim 1 half tartrate crystal form, wherein, half tartrate is The tartrates of L- half.
- 4. Yi Ligelusita as claimed in claim 1 half tartrate crystal form, wherein, the crystal form DSC collection of illustrative plates, which is shown at 161 DEG C ~ 162 DEG C, endothermic peak.
- 5. a kind of method of the tartrate crystal forms of Yi Ligelusita half prepared as described in claim any one of 1-4, It is characterized in that step is as follows, mixed solution is prepared, takes a certain amount of L-TARTARIC ACID to be dissolved in a certain amount of mixed solution, is heated to Solid dissolving；Take a certain amount of Yi Ligelusita to be dissolved in another a certain amount of mixed solution again, it is molten that above-mentioned L-TARTARIC ACID is added dropwise Liquid, stirring and crystallizing, filtering, is drying to obtain at room temperature.
- 6. preparation method as claimed in claim 5, wherein, the mixed solution is selected from methanol, acetone, water, ethanol, isopropanol In any two kinds.
- 7. preparation method as claimed in claim 5, wherein, one kind in the mixed solution is acetone soln.
- 8. preparation method as claimed in claim 5, wherein, the mixed solution is the mixed solution of water and acetone.
- 9. preparation method as claimed in claim 5, wherein, the drying temperature is 50-70 DEG C.
- 10. a kind of pharmaceutical composition, it includes half tartaric acid selected from the Yi Ligelusita described in claim any one of 1-4 Salt crystal form, and pharmaceutically acceptable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610375158.6A CN107445938B (en) | 2016-05-31 | 2016-05-31 | Crystalline form of eliglutacoside hemitartrate, process for its preparation and pharmaceutical compositions containing it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610375158.6A CN107445938B (en) | 2016-05-31 | 2016-05-31 | Crystalline form of eliglutacoside hemitartrate, process for its preparation and pharmaceutical compositions containing it |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107445938A true CN107445938A (en) | 2017-12-08 |
| CN107445938B CN107445938B (en) | 2020-04-03 |
Family
ID=60485864
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610375158.6A Active CN107445938B (en) | 2016-05-31 | 2016-05-31 | Crystalline form of eliglutacoside hemitartrate, process for its preparation and pharmaceutical compositions containing it |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107445938B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110878079A (en) * | 2018-12-31 | 2020-03-13 | 北京启慧生物医药有限公司 | Preparation method of high-purity eliagliptat |
| US10888547B2 (en) | 2009-11-27 | 2021-01-12 | Genzyme Corporation | Amorphous and a crystalline form of genz 112638 hemitartrate as inhibitor of glucosylceramide synthase |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102712629A (en) * | 2009-11-27 | 2012-10-03 | 基酶有限公司 | An amorphous and a crystalline form of Genz 112638 hemitartrat as inhibitor of glucosylceramide synthase |
-
2016
- 2016-05-31 CN CN201610375158.6A patent/CN107445938B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102712629A (en) * | 2009-11-27 | 2012-10-03 | 基酶有限公司 | An amorphous and a crystalline form of Genz 112638 hemitartrat as inhibitor of glucosylceramide synthase |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10888547B2 (en) | 2009-11-27 | 2021-01-12 | Genzyme Corporation | Amorphous and a crystalline form of genz 112638 hemitartrate as inhibitor of glucosylceramide synthase |
| US11458119B2 (en) | 2009-11-27 | 2022-10-04 | Genzyme Corporation | Amorphous and a crystalline form of genz 112638 hemitartrate as inhibitor of glucosylceramide synthase |
| CN110878079A (en) * | 2018-12-31 | 2020-03-13 | 北京启慧生物医药有限公司 | Preparation method of high-purity eliagliptat |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107445938B (en) | 2020-04-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105753872B (en) | Two spiropiperidines or spiropyrrolidines derivatives | |
| CN104650091B (en) | The micronization of ticagrelor and crystal formation thereof, and preparation method and medicinal application | |
| CN105769792A (en) | A tablet containing a 1-(beta-D-glucopyranosyl)-3-(phenylthienylmethyl)benzene compound | |
| KR20120113285A (en) | Polymorphs of dasatinib, preparation methods and pharmaceutical compositions thereof | |
| CN103936725B (en) | The C crystal form of canagliflozin and crystallization preparation method thereof | |
| CN101605767A (en) | The method for preparing piperazinyl phenyl carboxamides derivatives and Diazesuberane yl-benzamide derivatives | |
| CN103570621B (en) | Preparation method of (-)-huperzine A | |
| CN107445938A (en) | Crystal form, preparation method and the Pharmaceutical composition containing the crystal form of the tartrates of Yi Ligelusita half | |
| CN104364248B (en) | Methanesulfonic acid fluorine imatinib crystal formation and its production and use | |
| CN104955801B (en) | Substituted diaryl sulfonamide and application thereof | |
| CN105801568B (en) | One maleate crystal form of Afatinib and preparation method thereof and pharmaceutical composition | |
| CN105985394A (en) | Novel sofosbuvir crystal form and preparation method thereof | |
| CN1443178A (en) | (R)-N-[5-methyl-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydro-2-naphtyl] -4-morpholibenzamide | |
| CN102351812B (en) | Methanesulfonic acid cinepazide crystal form III and preparation method thereof | |
| CN103191051B (en) | Nelarabine injection composition and preparation method thereof | |
| CN105884680A (en) | Pirfenidone derivative and preparation method and use thereof | |
| CN104045598B (en) | Thiourea compounds containing arylamine structure, and preparation method and application thereof | |
| CN110167535A (en) | Pharmaceutical composition comprising oxazines derivative and its purposes in treatment or prevention Alzheimer disease | |
| CN107235973A (en) | The preparation method of the adjoining fluorobenzene calcium composition of piperidones chain with pharmaceutical activity | |
| CN104086531B (en) | A kind of Esomeprazole sodium compound and its pharmaceutical composition | |
| CN107556294A (en) | A kind of new anti-fungal infection medicine and its production and use | |
| CN108658843B (en) | Acetylbenzylamine piperidine amide derivative and application thereof as cerebral nerve protective agent | |
| CN110049765B (en) | Combination, application and treatment method thereof | |
| CN105998018A (en) | Application of pirfenidone derivative to pharmacy | |
| CN102267952B (en) | Quinazoline compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 102609 Beijing Daxing District biomedical industry base No. 26, Zhongguancun medical instrument garden 16, wing Wan West Road. Applicant after: Beijing Qihui Biomedical Co., Ltd. Address before: 102609 Beijing Daxing District biomedical industry base No. 26, Zhongguancun medical instrument garden 16, wing Wan West Road. Applicant before: Beijing Rev Medical Instrument Co., Ltd. |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210422 Address after: 102609 No.401, building 16, Zhongguancun medical equipment Park, No.26 Yongwang West Road, Daxing District biological medicine industrial base, Beijing Patentee after: BEIJING KAILAI TIANCHENG MEDICINE TECHNOLOGY Co.,Ltd. Address before: 102609 Beijing City, Daxing District biological medicine industry base AEON Road No. 26 Hospital of Zhongguancun Medical Park Building No. 16 Patentee before: Beijing Qihui Biomedical Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220525 Address after: 102609 Beijing Daxing District biomedical industry base No. 26, Zhongguancun medical instrument garden 16, wing Wan West Road. Patentee after: Beijing Qihui Biomedical Co.,Ltd. Address before: 102609 Room 401, building 16, Zhongguancun medical instrument Park, No. 26, Yongwang West Road, biological medicine industrial base, Daxing District, Beijing Patentee before: BEIJING KAILAI TIANCHENG MEDICINE TECHNOLOGY CO.,LTD. |
|
| TR01 | Transfer of patent right |